The purpose of the proposed project is the investigation of the mechanism of action of 7H-dibenzo(c,g)carbazole (DBC), an N-heterocyclic aromatic hydrocarbon which has been isolated in substantial quantities from cigarette tar. This compound is an extremely potent respiratory tract carcinogen in the Syrian golden hamster. DBC-induced respiratory tract carcinomas in this species closely resemble human lung cancers believed to be caused by exposure to environmental carcinogens. The proposed study will investigate the nature of the covalent interactions of N-heterocyclics with nucleic acids using DBC as a model compound. The extent of DBC binding to various polynucleotides and to DNA will be assessed by radiolabel techniques in in vitro rat and hamster microsomal systems and in hamster tracheal organ culture. DBC binding will be compared with benzo(a)pyrene (BaP) binding in these systems to determine how this parameter related to in vivo carcinogenicity of the two compounds. (DBC appears to be a more potent respiratory tract carcinogen that BaP in the hamster.) In addition, DBC-nucleotide adducts will be isolated from the microsomal system and characterized by fluorescence spectroscopy in an effort to determine whether epoxide intermediates are involved in DBC-DNA binding. A very important aspect in the elucidation of the mechanism of action of chemical carcinogens is an understanding of the fate of the carcinogen itself and the nature of its intracellular interactions. The nature of covalent interactions of N-heterocyclics with DNA has not been investigated. The overall objective of the proposed research is the characterization of DBC-DNA binding in an effort to understand the mechanism by which these agents induce cancer of the respiratory tract.